Synthesis of molecular hybrids derived from 4-quinolones as potential drug candidates to treat Alzheimer's Disease

• Grant number: 13/18203-5
• Support Opportunities: Regular Research Grants
• Start date: December 01, 2013
• End date: February 29, 2016
• Field of knowledge: Health Sciences - Pharmacy
• Principal Investigator: Wanda Pereira Almeida
• Grantee: Wanda Pereira Almeida
• Host Institution: Instituto de Química (IQ). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

The aim of this project is to identify potential drug candidates to treat Alzheimer´s disease (AD). In this way, we propose the synthesis of a series of N-acylhydrazone and piperazine derivatives of 3-carboethoxy-4-quinolone, as well the evaluation of their effects on the acetylcholinesterase (AChE) activity and aggregation of the beta-amyloid peptide, an important biomarker of AD. Our purpose is based on previous studies performed by our research group, which demonstrated that the cited quinolone inhibits the beta-amyloid aggregation and has a moderate effect on the AChE activity. Piperazine derivatives have a structural moiety smilar to donepezil, a known AChE inhibitor. In this drug, the mentioned subunit binds to the catalytic site of the enzyme. Regarding N-acylhydrazone derivatives, the hydrazone group is able to chelate metals and is part of several bioactive compounds. The activity of these compounds is related to the presence of N-acyl-hydrazone portion. Our synthetic strategy relies on a short step sequence, which has been employed in our laboratory to prepare a sort of substituted 4-quinolones. The biological evaluations will be done by following well-established protocols in the literature and in our research group. (AU)

Scientific publications

(4)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

GOMES, RALPH C.; SAKATA, RENATA P.; ALMEIDA, WANDA P.; COELHO, FERNANDO. Spirocyclohexadienones as an Uncommon Scaffold for Acetylcholinesterase Inhibitory Activity. Medicinal Chemistry, v. 15, n. 4, p. 373-382, 2019. (13/10449-5, 13/18203-5)

DANIELA P. GOUVÊA; GABRIELE A. BERWALDT; PATRÍCIA D. NEUENFELDT; RICARDO J. NUNES; WANDA P. ALMEIDA; WILSON CUNICO. Synthesis of Novel 2-Aryl-3-(2-morpholinoethyl)-1,3-thiazinan-4-ones Via Ultrasound Irradiation. Journal of the Brazilian Chemical Society, v. 27, n. 6, p. 1109-1115, 2016-06-00. (13/18203-5)

DA SILVA, GISELE S.; FIGUEIRO, MICHELI; TORMENA, CLAUDIO F.; COELHO, FERNANDO; ALMEIDA, WANDA P.. Effects of novel acylhydrazones derived from 4-quinolone on the acetylcholinesterase activity and A beta 42 peptide fibrils formation. Journal of Enzyme Inhibition and Medicinal Chemistry, v. 31, n. 6, p. 1464-1470, 2016. (13/18203-5)

SAKATA, RENATA P.; FIGUEIRO, MICHELI; KAWANO, DANIEL F.; ALMEIDA, WANDA P.. Effect on Acetylcholinesterase and Anti-oxidant Activity of Synthetic Chalcones having a Good Predicted Pharmacokinetic Profile. Medicinal Chemistry, v. 13, n. 7, p. 654-663, 2017. (13/18203-5)